Effects of depletion of intracellular tetrahydrobiopterin (BH4) in murine erythroleukemia cells have been investigated to understand its possible roles in cell proliferation and differentiation of erythroid cells. The results of inhibition of GTP cyclohydrolase, the first and rate-limiting enzyme in biosynthesis of BH4, have been compared with that of inhibition of sepiapterin reductase, another enzyme in BH4 biosynthesis. Reversal of the processes by repletion of cellular BH4 with biopterin related compounds has also been examined.